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Class-Switch Recombination Occurs Infrequently in Germinal Centers.
Immunity ( IF 32.4 ) Pub Date : 2019-07-30 , DOI: 10.1016/j.immuni.2019.07.001
Jonathan A Roco 1 , Luka Mesin 2 , Sebastian C Binder 3 , Christian Nefzger 4 , Paula Gonzalez-Figueroa 1 , Pablo F Canete 1 , Julia Ellyard 1 , Qian Shen 1 , Philippe A Robert 3 , Jean Cappello 1 , Harpreet Vohra 1 , Yang Zhang 5 , Carla R Nowosad 2 , Arien Schiepers 2 , Lynn M Corcoran 6 , Kai-Michael Toellner 5 , Jose M Polo 4 , Michael Meyer-Hermann 7 , Gabriel D Victora 2 , Carola G Vinuesa 8
Affiliation  

Class-switch recombination (CSR) is a DNA recombination process that replaces the immunoglobulin (Ig) constant region for the isotype that can best protect against the pathogen. Dysregulation of CSR can cause self-reactive BCRs and B cell lymphomas; understanding the timing and location of CSR is therefore important. Although CSR commences upon T cell priming, it is generally considered a hallmark of germinal centers (GCs). Here, we have used multiple approaches to show that CSR is triggered prior to differentiation into GC B cells or plasmablasts and is greatly diminished in GCs. Despite finding a small percentage of GC B cells expressing germline transcripts, phylogenetic trees of GC BCRs from secondary lymphoid organs revealed that the vast majority of CSR events occurred prior to the onset of somatic hypermutation. As such, we have demonstrated the existence of IgM-dominated GCs, which are unlikely to occur under the assumption of ongoing switching.



中文翻译:

类转换重组在生发中心很少发生。

类别转换重组 (CSR) 是一种 DNA 重组过程,它取代了免疫球蛋白 (Ig) 恒定区以形成最能抵御病原体的同种型。CSR 的失调可导致自身反应性 BCR 和 B 细胞淋巴瘤;因此,了解企业社会责任的时间和地点很重要。尽管 CSR 在 T 细胞启动时开始,但它通常被认为是生发中心 (GC) 的标志。在这里,我们使用了多种方法来证明 CSR 在分化为 GC B 细胞或浆母细胞之前被触发,并且在 GC 中大大减少。尽管发现一小部分 GC B 细胞表达种系转录本,但来自次级淋巴器官的 GC BCR 的系统发育树显示,绝大多数 CSR 事件发生在体细胞超突变发生之前。因此,

更新日期:2019-07-31
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